A 62-year-old woman has painless axillary and inguinal lymphadenopathy noticed over 8 months. Node biopsy shows a nodular architecture composed predominantly of small cleaved centrocytes. Immunohistochemistry shows aberrant nuclear BCL2 expression within germinal centres. What is the underlying pathogenesis?
- A Constitutive activation of JAK2 kinase
- B Loss of TP53 with uncontrolled proliferation
- C Juxtaposition of BCL2 to the IgH enhancer, blocking apoptosis ✓
- D Overexpression of cyclin D1 from t(11;14)
Correct answer: C. Juxtaposition of BCL2 to the IgH enhancer, blocking apoptosis
Explanation
Follicular lymphoma is defined by t(14;18), which places the anti-apoptotic BCL2 gene under control of the immunoglobulin heavy chain enhancer. Normal germinal centre C cells downregulate BCL2 to permit apoptosis of non-productive clones, so its persistence marks neoplastic follicles and distinguishes them from reactive follicular hyperplasia, which is BCL2 negative. Cyclin D1 overexpression belongs to mantle cell lymphoma, and JAK2 mutation belongs to myeloproliferative neoplasms.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.